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Background: In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the preclinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC. Findings: 96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43-1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61-1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab. Conclusions: In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.
RESUMEN
BACKGROUND: The comparative effectiveness study (ClinicalTrials.gov, NCT03016403) assessed the effects of a stepped-care intervention versus usual care on mental health outcomes, including anxiety, depression, coping self-efficacy, emotional distress (anxiety and depression combined), health-related quality of life (HRQoL), and perceived stress among underserved patients (i.e., low-income, uninsured, underinsured) with lung cancer (LC) and head-and-neck cancer (HNC). METHODS: In a randomized controlled trial, we investigated if 147 patients who received the stepped-care intervention had better mental health outcomes compared to 139 patients who received usual care. Using an intent-to-treat approach, we analyzed outcomes with linear mixed models. RESULTS: For the primary outcomes estimated mean differences (denoted by "Δ"), depression (Δ = 1.75, 95% CI = 0.52, 2.98, p = 0.01) and coping self-efficacy (Δ = -15.24, 95% CI = -26.12, -4.36, p = 0.01) were better for patients who received the intervention compared to patients who received usual care, but anxiety outcomes were not different. For secondary outcomes, emotional distress (Δ = 1.97, 95% CI: 0.68, 3.54, p =< 0.01) and HRQoL (Δ = -4.16 95% CI: -7.45, -0.87, p = 0.01) were better for patients who received the intervention compared to usual care patients, while perceived stress was not different across groups. CONCLUSIONS: The stepped-care intervention influenced depression and coping self-efficacy, important outcomes for patients with acute illnesses like LC and HNC. Although differences in emotional distress met the minimally important differences (MID) previously reported, depression and HRQoL were not above the MID threshold. Our study is among a few to report differences in mental health outcomes for underserved LC and HNC patients after receiving a psychological intervention. GOV IDENTIFIER: NCT03016403.
